Long noncoding RNA LINC00675 enhances phosphorylation of vimentin on Ser83 to suppress gastric cancer progression
Long noncoding RNA LINC00675 enhances phosphorylation of vimentin on Ser83 to suppress gastric cancer progression
复制标题
长非编码RNA LINC00675增强波形蛋白Ser83上的磷酸化以抑制胃癌进展
DOI：
10.1016/j.canlet.2017.10.026
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发表时间：
2018-01-01
期刊：
影响因子：
9.7
通讯作者：
Yang, Shi-Ming
中科院分区：
文献类型：
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作者：
Zeng, Shuo;Xie, Xia;Yang, Shi-Ming
长链非编码rna （IncRNAs）在癌症发展中起着至关重要的作用，但很少有IncRNAs在胃癌（GC）中被功能表征。本研究中，我们报道了一种IncRNA LINC00675，其在胃癌组织中的表达与邻近非肿瘤组织相比显著降低，其低表达与胃癌患者的低生存率相关。功能得失研究表明，LINC00675在体外抑制胃癌细胞的增殖、迁移和侵袭，在体内也抑制胃癌细胞的远端肺转移和肝转移，是一种肿瘤抑制因子。机制研究表明，LINC00675与参与细胞转移的蛋白vimentin相互作用，提高其Ser83磷酸化水平，导致GC细胞中vimentin丝的崩溃，从而减少细胞转移。综上所述，我们的研究结果表明，LINC00675的表达特征可能作为胃癌诊断和预后的一种新的生物标志物，同时也强调了LINC00675/vimentin复合物可能是胃癌的潜在治疗靶点。(C) 2017 Elsevier B.V.版权所有
Long noncoding RNAs (IncRNAs) play a crucial role in cancer development, but few IncRNAs have been functionally characterized in gastric cancer (GC). Here, we reported an IncRNA LINC00675 whose expression was significantly decreased in GC tissues compared with the adjacent non-tumor tissues, and its low expression was associated with the poor survival of GC patients. Gain-and loss-of-function studies indicated that LINC00675 was a tumor suppressor because it repressed the proliferation, migration and invasion of GC cells in vitro and also inhibited the distal pulmonary and hepatic metastases of GC cells in vivo. Mechanistic investigations revealed that LINC00675 interacted with vimentin, a protein involved in cell metastasis, and enhanced its phosphorylation level on Ser83 to result in the collapse of vimentin filament in GC cells, thereby reducing cell metastasis. Taken together, our findings indicate that LINC00675 expression signature may serve as a novel biomarker for the diagnosis and prognosis of GC, and also highlight that LINC00675/vimentin complex may be a potentially therapeutic target of GC. (C) 2017 Elsevier B.V. All rights reserved.